Calcium modulates the tethering of BCOR-PRC1.1 enzymatic core to KDM2B via liquid-liquid phase separation.

Recruitment of non-canonical BCOR-PRC1.1 to non-methylated CpG islands via KDM2B plays a fundamental role in transcription control during developmental processes and cancer progression. However, the mechanism is still largely unknown on how this recruitment is regulated. Here, we unveiled the importance of the Poly-D/E regions within the linker of BCOR for its binding to KDM2B. Interestingly, we also demonstrated that these negatively charged Poly-D/E regions on BCOR play autoinhibitory roles in liquid-liquid phase separation (LLPS) of BCORANK-linker-PUFD/PCGF1RAWUL. Through neutralizing negative charges of these Poly-D/E regions, Ca2+ not only weakens the interaction between BCOR/PCGF1 and KDM2B, but also promotes co-condensation of the enzymatic core of BCOR-PRC1.1 with KDM2B into liquid-like droplet. Accordingly, we propose that Ca2+ could modulate the compartmentation and recruitment of the enzymatic core of BCOR-PRC1.1 on KDM2B target loci. Thus, our finding advances the mechanistic understanding on how the tethering of BCOR-PRC1.1 enzymatic core to KDM2B is regulated.

Bacillus licheniformis suppresses Clostridium perfringens infection via modulating inflammatory response, antioxidant status, inflammasome activation and microbial homeostasis in broilers.

Pathogenic bacteria infection, especially Clostridium perfringens (C. perfringens), markedly threatened the health of animals, and further caused huge economic loss. In this study, Bacillus licheniformis HJ0135 (BL) was used. Oxford cup bacteriostatic test and inhibitory rate test were conducted to evaluate the antibacterial ability of BL. Results showed the strongest inhibitory role of BL on C. perfringens (P < 0.05). Afterwards, 540 one-day-old yellow-feather broilers (32.7 ± 0.2 g) were randomly allocated into 3 groups, including CON group (basal diet), CP group (basal diet + 1 × 109 CFU C. perfringens in gavage), and BL + CP group (basal diet containing 7.5 × 106 CFU/g BL + 1 × 109 CFU C. perfringens in gavage). At d 70, broilers in the CP and BL + CP groups were treated with C. perfringens by continuously oral administration for 5 d. The experiment lasted for 75 d. The serum, immune organs, jejunal mucosa, and cecal contents were collected for analysis. In vivo experiment showed that BL supplementation markedly improved (P < 0.05) BW, ADG, thymus index, serum immunoglobins and antioxidases, reduced feed conversion ratio (FCR) and serum pro-inflammatory cytokines of C. perfringens-infected broilers. Furthermore, the increased jejunal injury and levels of pro-inflammatory cytokines, decreased gene expressions of tight junction proteins in the jejunal mucosa were significantly alleviated (P < 0.05) by BL. More importantly, the activation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome was inhibited (P < 0.05) by BL to further attenuate jejunal damage. Besides, BL supplementation markedly increased (P < 0.05) the cecal isobutyric acid and isovaleric acid. Microbial analysis showed that BL changed the composition and relative abundances of microbiota in the cecal contents (P < 0.05), especially the short chain fatty acids (SCFAs)-producing bacteria including Eubacterium_coprostanoligenes_group, Megamonas, Faecalibacterium, and Lactobacillus, which further protected against C. perfringens-induced jejunal inflammation in broilers. Our study laid a theoretical basis for the application of probiotics in lessening C. perfringens-related diseases in poultry farming.

Effects of rhamnolipid replacement of chlortetracycline on growth performance, slaughtering traits, meat quality and antioxidant function in broilers.

BACKGROUND: Rhamnolipids (RLS) are surfactants that improve the growth performance of poultry by improving the absorption of nutrients. This study aims to investigate the effects of RLS replacement of chlortetracycline (CTC) on growth performance, slaughtering traits, meat quality, antioxidant function and nuclear-factor-E2-related factor 2 (Nrf2) signaling pathway in broilers. A total of 600 one-day-old Arbor Acres chicks were randomly assigned to five groups with eight replicates in each group, raised for 42 days. Broilers were respectively fed a basal diet with no CTC or RLS, 75 mg kg-1 CTC, and 250, 500, 1000 mg kg-1 RLS. RESULTS: Dietary supplementation with RLS linearly increased the average daily gain, average daily feed intake, carcass yield, eviscerated yield, ether extract, enhanced total superoxide and glutathione peroxidase (GPx) activities, overexpressed the relative expressions of Nrf2, heme oxygenase 1, Copper/zinc superoxide dismutase, Manganese superoxide dismutase, GPx and catalase and decreased the lightness value at 24 h, drip loss and malondialdehyde contents of broilers (P < 0.05). Compared with the control group, broilers fed 1000 mg kg-1 RLS reduced the drip loss and broilers fed 500 mg kg-1 RLS increased muscle crude fat content (P < 0.05). Compared with the CTC group, dietary supplementation with 1000 mg kg-1 RLS increased eviscerated yield (P < 0.05). CONCLUSION: RLS could improve growth performance, crude fat content, meat quality and antioxidant capacity and activate relative expression of genes in the Nrf2 signaling pathway in broilers. It could be used as an antibiotic substitute in diets and the recommended supplemental dose of RLS in feed of broilers is 1000 mg kg-1. © 2024 Society of Chemical Industry.

Early identification of hepatocellular carcinoma patients at high-risk of recurrence using the ADV score: a multicenter retrospective study.

BACKGROUND: Postoperative recurrence is a vital reason for poor 5-year overall survival in hepatocellular carcinoma (HCC) patients. The ADV score is considered a parameter that can quantify HCC aggressiveness. This study aimed to identify HCC patients at high-risk of recurrence early using the ADV score. METHODS: The medical data of consecutive HCC patients undergoing hepatectomy from The First Affiliated Hospital of Nanjing Medical University (TFAHNJMU) and Nanjing Drum Tower Hospital (NJDTH) were retrospectively reviewed. Based on the status of microvascular invasion and the Edmondson-Steiner grade, HCC patients were divided into three groups: low-risk group (group 1: no risk factor exists), medium-risk group (group 2: one risk factor exists), and high-risk group (group 3: coexistence of two risk factors). In the training cohort (TFAHNJMU), the R package nnet was used to establish a multi-categorical unordered logistic regression model based on the ADV score to predict three risk groups. The Welch's T-test was used to compare differences in clinical variables in three predicted risk groups. NJDTH served as an external validation center. At last, the confusion matrix was developed using the R package caret to evaluate the diagnostic performance of the model. RESULTS: 350 and 405 patients from TFAHNJMU and NJDTH were included. HCC patients in different risk groups had significantly different liver function and inflammation levels. Density maps demonstrated that the ADV score could best differentiate between the three risk groups. The probability curve was plotted according to the predicted results of the multi-categorical unordered logistic regression model, and the best cut-off values of the ADV score were as follows: low-risk ≤ 3.4 log, 3.4 log < medium-risk ≤ 5.7 log, and high-risk > 5.7 log. The sensitivities of the ADV score predicting the high-risk group (group 3) were 70.2% (99/141) and 78.8% (63/80) in the training and external validation cohort, respectively. CONCLUSION: The ADV score might become a valuable marker for screening patients at high-risk of HCC recurrence with a cut-off value of 5.7 log, which might help surgeons, pathologists, and HCC patients make appropriate clinical decisions.

Pembrolizumab plus chemotherapy in frontline treatment of advanced ovarian cancer: Clinical and translational results from a phase 2 trial.

BACKGROUND: The efficacy and feasibility of pembrolizumab combined with chemotherapy in frontline management of advanced high-grade epithelial ovarian cancer (EOC) is unknown. Additionally, modification of the tumor microenvironment following neoadjuvant therapy is not well understood. METHODS: In this single-arm phase 2 trial (this study was registered at ClinicalTrials.gov: NCT02520154), eligible patients received up to 4 cycles of neoadjuvant chemotherapy followed by interval cytoreduction, 3 cycles of adjuvant intravenous carboplatin/weekly paclitaxel/pembrolizumab, and finally maintenance pembrolizumab until progression or toxicity (maximum 20 cycles). The primary endpoint was progression-free survival (PFS). Secondary endpoints included feasibility, toxicity, and overall survival (OS). PD-L1 staining, multiplex immunofluorescence staining, RNA sequencing, reverse-phase protein array analyses were performed on pre- and post-chemotherapy samples. FINDINGS: Thirty-one eligible patients were enrolled. Median PFS and OS was 14.88 (95% CI 12.39-23.00) and 57.43 months (95% CI 30.88-not reached), respectively. Among those with PD-L1 combined positive score (CPS) ≥10, the median PFS and OS were not reached compared to those with CPS <10 (10.50 and 30.90 months, respectively). Feasibility was met, with all patients completing their planned adjuvant cycles. Treatment discontinuation due to immune-related toxicity occurred in 6 patients (20%). Chemotherapy resulted in an infiltration of anti-tumor immune cells in the tumor microenvironment. Samples of patients with the best PFS demonstrated increased expression of NF-κB, TGF-ß, and ß-catenin signaling. CONCLUSIONS: Pembrolizumab with chemotherapy was feasible and resulted in PFS within the historical range for this EOC population. Patients with CPS ≥10 may benefit more from this regimen, and future studies should investigate this potential biomarker. FUNDING: This investigator-initiated trial was funded by Merck.

Near-Infrared Responsive Biomimetic Titanate/TiO2-X Heterostructure: A Therapeutic Strategy for Combating Implant-Associated Infection and Enhancing Osseointegration.

Implant-associated infections and delayed osseointegration are major challenges for the clinical success of titanium implants. To enhance antibacterial effects and promote early osseointegration, we developed a synergistic photothermal (PTT)/photodynamic (PDT) therapy strategy based on near-infrared (NIR) responsive biomimetic micro/nano titanate/TiO2-X heterostructure coatings (KMNW and NaMNS) in situ constructed on the surface of titanium implants. Specifically, KMNW and NaMNS significantly enhanced photothermal conversion capabilities, achieving localized high temperatures of 48-51 °C and promoting substantial amounts of reactive oxygen species production under 808 nm irradiation. In vitro antibacterial experiments demonstrated that KMNW achieved the highest antibacterial rates against Staphylococcus aureus and Escherichia coli, at 98.78 and 98.33% respectively. Moreover, by mimicking the three-dimensional fibrous network of the extracellular matrix during bone healing, both KMNW and NaMNS markedly promoted the proliferation and osteogenic differentiation of osteoblasts. In vivo implantation studies further confirmed these findings, with KMNW and NaMNS exhibiting superior antibacterial performance under NIR irradiation─94.45% for KMNW and 92.66% for NaMNS. Moreover, KMNW and NaMNS also significantly promoted new bone formation and improved osseointegration in vivo. This study presents a promising PTT/PDT therapeutic strategy for dentistry and orthopedics by employing NIR-responsive biomimetic coatings to combat implant-associated infection and accelerate osseointegration.

Critical roles of low-molecular-weight organic acid in enhancing hydroxyl radical production by ferrous oxidation on γ-Al2O3 mineral surface.

Recognizing the pervasive presence of alumina minerals and low-molecular-weight organic acids (LMWOAs) in the environment, this study addressed the gap in the interaction mechanisms within the ternary system involving these two components and Fe(II). Specifically, the impacts of LMWOAs on hydroxyl radicals (•OH) production and iron species transformation during Fe(II) oxidation on γ-Al2O3 mineral surface were examined. Results demonstrated that adding 0.5 mM oxalate (OA) or citrate (CA) to the γ-Al2O3/Fe(II) system (28.1 µM) significantly enhanced •OH production by 1.9-fold (51.9 µM) and 1.3-fold (36.2 µM), respectively, whereas succinate (SA) exhibited limited effect (30.7 µM). Raising OA concentration to 5 mM further promoted •OH yield to 125.0 µM after 24 h. Deeper analysis revealed that CA facilitated the dissolution of adsorbed Fe(II) and its subsequent oxygenation by O2 through both one- and two-electron transfer mechanisms, whereas OA enhanced the adsorption of dissolved Fe(II) and more efficient two-electron transfer for H2O2 production. Additionally, LMWOAs presence favored the formation of iron minerals with poor crystallinity like ferrihydrite and lepidocrocite rather than well-crystallized forms such as goethite. The distinct impacts of various LMWOAs on Fe(II) oxidation and •OH generation underscore their unique roles in the redox processes at mineral surface, consequently modulating the environmental fate of prototypical pollutants like phenol.

Development and evaluation of a candidate reference measurement procedure for detecting 17α-hydroxyprogesterone in dried blood spots using isotope dilution liquid chromatography tandem mass spectrometry.

17α-Hydroxyprogesterone (17α-OHP) quantification in dried blood spots (DBS) is essential for newborn screening for congenital adrenal hyperplasia (CAH), which is challenging due to its low physiological concentration. The high false-positive rates of immunoassays necessitate the development of more accurate methods. Liquid chromatography tandem mass spectrometry (LC-MS/MS) offers increased specificity and sensitivity, yet standardized procedures for 17α-OHP measurement are required for clinical application. A candidate reference measurement procedure (cRMP) using isotope dilution LC-MS/MS was developed for 17α-OHP quantification in DBS. By utilizing stable isotope-labeled D8-17α-OHP as an internal standard, the cRMP was optimized, covering sample preparation, calibration, and LC-MS/MS analysis. The method performance was validated across several parameters, including precision, accuracy, specificity, detection limits, and matrix effects. Clinical applicability was further assessed through the establishment of reference intervals for healthy newborns. The developed cRMP exhibited a linear range of 1.00 to 80.00 ng/mL for 17α-OHP, with detection and quantification limits of 0.14 ng/mL and 0.52 ng/mL, respectively. Inter- and intraday precision demonstrated coefficients of variation within 1.27 to 5.69%. The recovery rates and matrix effects were well within acceptable limits, ensuring method reliability. Clinical application showed distinct reference intervals for healthy newborns that were unaffected by sex but influenced by weight and gestational age. This method significantly enhances CAH diagnostic accuracy in newborns, providing a valuable tool for clinical laboratories and improving newborn screening program standardization and traceability.

Understanding the variability of ground-level ozone and fine particulate matter over the Tibetan plateau with data-driven approach.

The Tibetan Plateau, known as the "Third Pole", is susceptible to ground-level ozone (O3) and fine particulate matter (PM2.5) pollution due to its unique high-altitude environment. This study constructed random forest regression models using multi-source data from ground measurements and meteorological satellites to predict variations in ground-level O3 and PM2.5 concentrations and their influencing factors across seven major cities in the Tibetan Plateau over two-year periods. The models successfully reproduced O3 and PM2.5 levels with satisfactory R-squared values of 0.71 and 0.73, respectively. Results reveal combustion-related carbon monoxide (CO) and nitrogen dioxide (NO2) as the most substantial influences on O3 and PM2.5 concentrations. Solar radiation, geographical factors, and meteorological variables also played crucial roles in driving pollutant variations. Conversely, transport-related and human activity factors exhibited relatively lower significance. High O3 and PM2.5 pollution occurred during pre-monsoon and post-monsoon/winter seasons, driven by solar radiation and emissions, respectively. While CO consistently contributed across cities and seasons, key influencing factors varied locally. This study unveils the key driving forces governing air pollutant variations across the Tibetan Plateau, shedding light on complex atmospheric processes in this unique high-altitude region.

Dietary Clostridium butyricum and 25-Hydroxyvitamin D3 modulate bone metabolism of broilers through the gut-brain axis.

Leg disorders have become increasingly common in broilers, leading to lower meat quality and major economic losses. This study evaluated the effects of dietary supplementation with Clostridium butyricum (C. butyricum) and 25-hydroxyvitamin D3 (25-OH-D3) on bone development by comparing growth performance, tibial parameters, Ca and P contents of tibial ash, bone development-related indicators' level, and cecal short-chain fatty acids in Cobb broilers. All birds were divided into four treatment groups, which birds fed either a basal diet (Con), basal diet + 75 mg chlortetracycline/kg (Anti), basal diet + C. butyricum at 109 CFU/kg (Cb), basal diet + C. butyricum at 109 CFU/kg and 25-OH-D3 at 25 µg/kg (CbD), or basal diet + 25-OH-D3 at 25 µg/kg (CD). Our results suggest that the dietary supplementation in Cb, CbD, and CD significantly increased the body weight (BW) and average daily gain (ADG), and reduced the feed-to-weight ratio (F/G) at different stages of growth (P < 0.05). Dietary supplementation in Cb, CbD, and CD prolonged (P < 0.05) the behavioral responses latency-to-lie (LTL) time, reduced (P < 0.05) the levels of osteocalcin (BGP) and peptide tyrosine (PYY), and increased (P < 0.05) serotonin (5-HT) and dopamine (DA). Treatment with Cb increased (P < 0.05) the levels of acetic acid, isobutyric acid, butyric acid, and isovaleric acid compared with those in Con group. The cecal metagenome showed that Alistipes spp. were significantly more abundant in Cb, CbD, and CD groups (P < 0.05). A total of 12 metabolic pathways were significantly affected by supplementation, including the signaling pathways of glucagon, insulin, and PI3K-AKT; primary and secondary bile acid biosynthesis; and P-type Ca 2+ transporters (P < 0.05). Hence, the CbD supplementation modulates bone metabolism by regulating the mediators of gut-brain axis, which may inform strategies to prevent leg diseases and improve meat quality in broilers.

Convenient determination of polystyrene microplastics in soils by gel permeation chromatography-ultraviolet detection analysis.

Microplastics (MPs), especially polystyrene microplastics (PS-MPs), have emerged a new worldwide pollutant, prompting significant public concern regarding their detection in environmental media. Analysis of PS-MPs in soil remains as a challenging task for analysts due to the highly intricate matrices. This work presents a practical approach for detecting PS-MPs in soil, which involves dilute HCl-assisted extraction and gel permeation chromatography- ultraviolet detection (GPC-UV) analysis. The presence of MPs in soil was confirmed through the use of a scanning electron microscope in conjunction with energy dispersive spectroscopy investigation. PS-MPs was isolated from soil, by agitating it with a diluted HCl solution, filtering the resulting liquid, and dissolving the residue on the filter with THF. The extractant was subsequently determined by GPC-UV. The introduction of a small amount of HCl into the extraction system was found to greatly expedite the settling of soil in water and enhance the efficacy of extracting PS-MPs in about 30 min. The linear range of PS-MPs was from 1.0 to 100 µg/mL with R2 > 0.999. Good reproducibility was obtained with the intra-day relative standard deviation (RSD, n = 3) of 1.36 % and the inter-day RSD (n = 3) of 4.78 %. The concentration of PS-MPs in soil samples were N.D. - 2.33 µg/g, and the good recoveries were 76.7-100.3 %. The corresponding AFGEEprer score was calculated to be 0.59, indicating the concept of green analytical chemistry for the pretreatment method. These results indicated that this method has a powerful potential for the accurate and rapid determination of PS-MPs in soil.

Generation of Polyploid Giant Cancer Cells (PGCCs) from Hey Ovarian Cancer Cells and Analysis of Embryonic Properties.

Polyploid giant cancer cells (PGCCs) play a fundamental role in tumor initiation, dormancy, drug resistance, and metastasis, although the detailed biology of PGCCs remains poorly understood. The lack of literature on establishing a reproducible in vitro system for generating PGCCs is the leading technological obstacle to studying the biology of PGCCs. Here we provide a detailed protocol for generating stable PGCCs from Hey cancer cells and studying the PGCCs' embryonic stemness. This protocol includes (1) generating PGCCs of high purity in 2D culture by exposing Hey cells to paclitaxel, monitoring the cell cycle and amitotic budding of daughter cells from PGCCs, and collecting and studying the daughter cells; (2) inducing PGCCs to form spheroids expressing embryonic stemness markers and observing the spheroids' cleavage and blastocyst-like structure; and (3) inducing redifferentiation of PGCCs into different lineages of differentiated cells.

A cuttlefish ink nanoparticle-reinforced biopolymer hydrogel with robust adhesive and immunomodulatory features for treating oral ulcers in diabetes.

Oral ulcers can be managed using a variety of biomaterials that deliver drugs or cytokines. However, many patients experience minimal benefits from certain medical treatments because of poor compliance, short retention times in the oral cavity, and inadequate drug efficacy. Herein, we present a novel hydrogel patch (SCE2) composed of a biopolymer matrix (featuring ultraviolet-triggered adhesion properties) loaded with cuttlefish ink nanoparticles (possessing pro-healing functions). Applying a straightforward local method initiates the formation of a hydrogel barrier that adheres to mucosal injuries under the influence of ultraviolet light. SCE2 then demonstrates exceptional capabilities for near-infrared photothermal sterilization and neutralization of reactive oxygen species. These properties contribute to the elimination of bacteria and the management of the oxidation process, thus accelerating the healing phase's progression from inflammation to proliferation. In studies involving diabetic rats with oral ulcers, the SCE2 adhesive patch significantly quickens recovery by altering the inflamed state of the injured area, facilitating rapid re-epithelialization, and fostering angiogenesis. In conclusion, this light-sensitive hydrogel patch offers a promising path to expedited wound healing, potentially transforming treatment strategies for clinical oral ulcers.

Redox-modulated SNX25 as a novel regulator of GPCR-G protein signaling from endosomes.

GPCR-G protein signaling from endosomes plays a crucial role in various physiological and pathological processes. However, the mechanism by which endosomal G protein signaling is terminated remains largely unknown. In this study, we aimed to investigate the regulatory mechanisms involved in terminating the signaling of Gα subunits from endosomes. Through structural analysis and cell-based assays, we have discovered that SNX25, a protein that targets endosomes via its PXA or PXC domain, interacts with regulator of G protein signaling (RGS) proteins (including RGS2, RGS4, RGS8, and RGS17) in a redox-regulated manner. The interaction between SNX25 and these RGS proteins enhances their GTPase-accelerating activity towards Gαi/q and their ability to bind GDP-bound (inactive form) Gαi/q. As a result, SNX25 recruits these RGS proteins to endosomes, leading to the termination of endosomal Gαi/q signaling. Furthermore, we have found that the SNX25/RGS complex also exerts a negative regulatory effect on Gαi/q signaling from the plasma membrane. This is achieved by recruiting Gαi/q to endosomes and preventing its activation on the plasma membrane. Our findings shed light on the previously unknown role of redox-modulated SNX25 in inhibiting Gαi/q signaling, thereby uncovering a novel mechanism for terminating Gαi/q signaling from endosomes. Importantly, this study expands our understanding of the regulation of GPCR-Gαi/q signaling beyond the plasma membrane.

Effects of bamboo leaf flavonoids on growth performance, antioxidants, immune function, intestinal morphology, and cecal microbiota in broilers.

BACKGROUND: Bamboo leaf flavonoids (BLF) are the main bioactive ingredients in bamboo leaves. They have antioxidant, anti-inflammatory, antibacterial, and other effects. In this study, the effects of dietary BLF on growth performance, immune response, antioxidant capacity, and intestinal microbiota of broilers were investigated. A total of 288 broilers were divided into three groups with eight replicates and 12 birds in each replicate. Broilers were fed a basic diet or the basic diet supplemented with 1000 or 2000 mg kg-1 BLF for 56 days. RESULTS: The results showed that supplementation of BLF increased body weight (BW) and average daily weight gain (ADG), and reduced average daily feed intake (ADFI) (P < 0.05). The serum immunoglobulin A (IgA), immunoglobulin M (IgM), and interleukin 10 (IL-10) content of broilers in the BLF1000 group was increased and the interleukin 1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) content was decreased (P < 0.05). The levels of IgM and IL-10 in jejunum mucosa were found to be enhanced by BLF (P < 0.05). The BLF1000 group exhibited a significant reduction in the concentration of TNF-α (P < 0.05). Serum and jejunum mucosa total antioxidant capacity (T-AOC) levels in the BLF1000 group were increased (P < 0.05). The serum catalase (CAT) and glutathione peroxidase (GSH-Px) effects of the BLF1000 group and serum CAT effects of BLF2000 group were increased (P < 0.05). The CON group demonstrated a lower relative abundance of Christensenellaceae_R-7_group and Oscillibacter than the BLF group (P < 0.05). CONCLUSION: Dietary BLF inclusion enhanced the growth performance, immune, and antioxidant functions, improved the intestinal morphology, and ameliorated the intestinal microflora structure in broiler. Adding 1000 mg kg-1 BLF to the broiler diet can be considered as an effective growth promoter. © 2024 Society of Chemical Industry.

Research progress of protein induced by vitamin K absence or antagonist II in liver transplantation for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common pathologic type of primary liver cancer. Liver transplantation (LT) is a radical strategy for treating patients with early-stage HCC, which may lead to a better prognosis compared to hepatectomy and ablation. However, survival of patients who develop HCC recurrence after LT is short, and early recurrence is the most common cause of death. Thus, efficient biomarkers are also needed in LT to guide precision therapy to improve patient prognosis and 5-year survival. Protein induced by vitamin K absence or antagonist II (PIVKA-II) is an abnormal prothrombin that cannot activate coagulation, and it is significantly increased in patients with HCC, obstructive jaundice, and those taking vitamin K antagonists. Over the past decades, substantial progress has been made in the study of PIVKA-II in diagnosing, surveilling, and treating HCC, but its role in LT still needs to be elaborated. In this review, we focused on the role of PIVKA-II as a biomarker in LT for HCC, especially its relationship with clinicopathologic features, early recurrence, long-term survival, and donor-recipient selection.

Oncogenic functions and therapeutic potentials of targeted inhibition of SMARCAL1 in small cell lung cancer.

Small cell lung cancer (SCLC) is a recalcitrant cancer characterized by high frequency loss-of-function mutations in tumor suppressors with a lack of targeted therapy due to absence of high frequency gain-of-function abnormalities in oncogenes. SMARCAL1 is a member of the ATP-dependent chromatin remodeling protein SNF2 family that plays critical roles in DNA damage repair and genome stability maintenance. Here, we showed that SMARCAL1 was overexpressed in SCLC patient samples and was inversely associated with overall survival of the patients. SMARCAL1 was required for SCLC cell proliferation and genome integrity. Mass spectrometry revealed that PAR6B was a downstream SMARCAL1 signal molecule which rescued inhibitory effects caused by silencing of SMARCAL1. By screening of 36 FDA-approved clinically available agents related to DNA damage repair, we found that an aza-anthracenedione, pixantrone, was a potent SMARCAL1 inhibitor which suppressed the expression of SMARCAL1 and PAR6B at protein level. Pixantrone caused DNA damage and exhibited inhibitory effects on SCLC cells in vitro and in a patient-derived xenograft mouse model. These results indicated that SMARCAL1 functions as an oncogene in SCLC, and pixantrone as a SMARCAL1 inhibitor bears therapeutic potentials in this deadly disease.

Mussel byssus-inspired dual-functionalization of zirconia dental implants for improved bone integration.

Zirconia faces challenges in dental implant applications due to its inherent biological inertness, which compromises osseointegration, a critical factor for the long-term success of implants that rely heavily on specific cell adhesion and enhanced osteogenic activity. Here, we fabricated a dual-functional coating that incorporates strontium ions, aimed at enhancing osteogenic activity, along with an integrin-targeting sequence to improve cell adhesion by mussel byssus-inspired surface chemistry. The results indicated that although the integrin-targeting sequence at the interface solely enhances osteoblast adhesion without directly increasing osteogenic activity, its synergistic interaction with the continuously released strontium ions from the coating, as compared to the release of strontium ions alone, significantly enhances the overall osteogenic effect. More importantly, compared to traditional polydopamine surface chemistry, the coating surface is enriched with amino groups capable of undergoing various chemical reactions and exhibits enhanced stability and aesthetic appeal. Therefore, the synergistic interplay between strontium and the functionally customizable surface offers considerable potential to improve the success of zirconia implantation.

Hydrated Calcium Vanadate Nanoribbons with a Stable Structure and Fast Ion Diffusion as a Cathode for Quasi-Solid-State Zinc-Ion Batteries.

We demonstrated the use of hydrated calcium vanadate (CaV6O16·3H2O, denoted as CaVO-2) as a cathode for aqueous zinc-ion batteries (AZIBs). Nanoribbons of hydrated calcium vanadate facilitated shortening of the Zn2+ transport distance and accelerated zinc-ion insertion. The introduction of interlayer structure water increased the interlayer spacing of calcium vanadate and as a "lubricant". Ca2+ insertion also expanded the interlayer spacing and further stabilized the interlayer structure of vanadium-based oxide. The density functional theory results showed that the introduction of Ca2+ and structured water could effectively improve the diffusion kinetics, resulting in the rapid transport of zinc ions. As a result, AZIBs based on the CaVO-2 cathode offered high specific capacity (329.6 mAh g-1 at 200 mA g-1) and fast charge/discharge capability (147 mAh g-1 at 10 A g-1). Impressively, quasi-solid-state zinc-ion batteries based on the CaVO-2 cathode and polyacrylamide-cellulose nanofiber hydrogel electrolytes maintained an outstanding specific capacity and long cycle life (162 mAh g-1 over 10 000 cycles at 5 A g-1). This study provided a reliable strategy for metal-ion insertion and the structural water introduction of oxides to produce a high-quality cathode for ZIBs. Meanwhile, it provides ideas for the combination of vanadium-based materials and gel electrolytes to construct solid-state zinc-ion batteries.